Intermediate filament (IF) proteins utilize central alpha-helical domains to generate polymeric fibers intermediate in size between actin microfilaments and microtubules. The regions flanking the central structural domains have diverged greatly to permit IF proteins to adopt specialized functions. Keratins represent the largest two groups of IF proteins. Most keratins serve structural functions in hair or epidermis. Intracellular epidermal keratins also provide strength to epithelial sheets. The intracellular type I keratins and other IF proteins are cleaved by caspases during apoptosis to ensure the disposal of the relatively insoluble cellular components. However, recent studies have also revealed an unexpected protective role for keratin 8 during TNF and Fas mediated apoptosis. Evidence for possible functions of keratins both upstream and downstream of apoptotic signaling are considered.